Small Cell Lung Cancer and Breast Cancer
Conditions
Brief summary
This study consists of two phases. The phase I study is designed to investigate the safety and tolerability of Satoreotide tetraxetan following fractionated i.v. administrations in pre-treated subjects with locally advanced or metastatic cancers expressing sstr2 as identified by Satoreotide trizoxetan Positron Emission Tomography (PET/CT) scans. This phase will encompass both radioactivity escalation and peptide mass dose evaluation. Phase II will assess the efficacy of Satoreotide tetraxetan in subjects in selected indications, in a basket design.
Interventions
Radioactivity delivered in 2 administrations (cycles): one loading dose followed by a lower maintenance dose, 6 weeks apart until progression or unacceptable toxicity (up to 4 additional cycles could be administered depending on efficacy and tolerability).
Imaging companion: 1 administration at screening and one administration at End of core Trial cycle.
Sponsors
Ipsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Consenting adults of Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 * Histologically confirmed locally advanced or metastatic disease which has progressed during or after, failed to respond to, or for which there is poor tolerability or after a contraindication to available Standard of Care (SoC) treatment options as per the assessment of the investigator; initially, subjects with the disease below may be considered: 1. Subjects who had Extensive Disease (ED-SCLC) at presentation who have progressed on or after one line standard chemotherapy. If a subject had Limited Disease (LD-SCLC) at presentation and received surgery and/or radiotherapy as first line treatment (with or without chemotherapy) and has localized relapse, further local treatment (such as surgery) should be considered in addition to the chemotherapy options; For subjects with either ED-SCLC or LD-SCLC, if subjects relapse more than 6 months after first-line treatment, re-treatment with their initial regimen is recommended. Subjects may have received prior immunotherapy. 2. Subjects with Human Epidermal Growth Factor Receptor (HR+)/(HER2-) metastatic BC after a failure of prior SoC-treatments and who have received, if indicated, at least one line of hormonal therapy, Cyclin-dependent kinase (CDK4/6) inhibitor and/or everolimus for advanced or metastatic disease and at least one line of chemotherapy for metastatic disease; subjects with a Breast Cancer (BRCA)-mutated metastatic disease who may have received a Poly adenosine diphosphate ribose polymerase (PARP) inhibitor, if available, are eligible; prior adjuvant hormonal treatment and prior adjuvant chemotherapy are allowed. * Documented progressive disease (radiological, based on RECIST v1.1) within 3 months prior to first study drug administration. Screening study-related images should be sent to the Imaging core laboratory (ICL). * Adequate organ function determined within 28 days prior to 177Lu-OPS201 administration, defined as follows: * Haematological: white blood cells (WBC) ≥3000/μL, with absolute neutrophil count ≥1000/μL, platelet ≥100,000/μL and haemoglobin ≥9 g/dL (without a need for hematopoietic growth factor or transfusion support). * Renal: Estimated glomerular filtration rate (eGFR) ≥55 mL/minute/1.73m2 * Hepatic: total serum bilirubin ≤2×ULN; aspartate aminotransferase/ alanine aminotransferase ≤2.5×ULN (≤5×ULN if a subject has liver metastases) * Formalin fixed paraffin embedded tumour sample (archival tumour sample obtained within 1 month prior to concent from the primary or metastatic lesion OR is willing to undergo newly obtained biopsy prior to the first dose of study treatment. Subjects who are unable or do not concent to provide acceptable tissue may not be enrolled unless there has been prior agreement with the sponsor. * 68Ga OPS202 uptake in the target tissue (a primary tumour, lymph nodes longest diameter on PET/CT as confirmed by a central reader. * Radiologically, ≥50% matching between the lesions detected on 68Ga OPS202-PET/CT and on 18F-fluorodeoxyglucose (18F-FDG)-PET/CT as confirmed by central reader
Exclusion criteria
* Male subjects with BC. * Unstable central nervous system metastasis * Centrally located lung tumours that show radiogical evidence (CT or MRI) of either: * cavitation or necrosis, or * focal invasion for major blood vessels. * Subjects had received chemotherapy within the previous 4 weeks or had not recovered from adverse events due to chemotherapy. Additional
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Tolerated Cumulative Activity - Phase I | From Day 1 (first administration of 177Lu-satoreotide tetraxetan) up to 6 weeks after the second administration; no longer applicable due to early study termination. |
| Objective Response Rate Over the Two Treatment Cycles - Phase II | 6 weeks after each administration of 177Lu-satoreotide tetraxetan during the core study or at occurrence of first clinical signs of disease progression as determined by the investigator, up to 90 days; no longer applicable due to early study termination. |
Countries
Austria, Belgium, France, Germany, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
This phase I/II, multicenter, open-label single-arm study of 177Lu-satoreotide tetraxetan therapy with companion diagnostic imaging Gallium-68 (68Ga)-satoreotide trizoxetan (formerly 68Ga-OPS202) positron emission tomography (PET)/computed tomography (CT) was terminated early on 20 November 2019 due to unsuccessful screening.
Pre-assignment details
Overall, 9 subjects were enrolled of which 8 received the screening investigational imaging product (IIP) 68Ga-satoreotide trizoxetan and 1 did not due to consent withdrawn by subject. None of the subjects received the therapeutic investigational radiopharmaceutical product (IRPP), 177Lu-satoreotide tetraxetan.
Participants by arm
| Arm | Count |
|---|---|
| Screened Subjects In the screening period, 8 subjects received a single i.v. injection of IIP, 68Ga-satoreotide trizoxetan with a peptide mass of up to 45 ug and a radioactivity dose range of 150-200 MBq for screening purposes. The PET images were acquired at 1-hour post injection and 1 contrast enhanced CT scan was performed. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Screen Failure | 8 |
Baseline characteristics
| Characteristic | Screened Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Maximum Tolerated Cumulative Activity - Phase I
Time frame: From Day 1 (first administration of 177Lu-satoreotide tetraxetan) up to 6 weeks after the second administration; no longer applicable due to early study termination.
Population: No efficacy data was collected since none of the subjects received the IRPP, 177Lu-satoreotide tetraxetan.
Primary
Objective Response Rate Over the Two Treatment Cycles - Phase II
Time frame: 6 weeks after each administration of 177Lu-satoreotide tetraxetan during the core study or at occurrence of first clinical signs of disease progression as determined by the investigator, up to 90 days; no longer applicable due to early study termination.
Population: No efficacy data was collected since none of the subjects received the IRPP, 177Lu-satoreotide tetraxetan.